Alpha-smooth muscle actin expression and structure integrity in chondrogenesis of human mesenchymal stem cells

Hung, Shih‐Chieh; Kuo, Pei-Yin; Chang, Ching-Fang; Chen, Tain-Hsiung; Ho, Larry L.T.

doi:10.1007/s00441-006-0156-x

Cited by 17 publications

(15 citation statements)

References 35 publications

(33 reference statements)

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“…Myofibroblastic properties have also been induced in bone marrow-derived MSCs in vitro (13). Increased expression of a-SMA and vimentin has been noted after 14 to 21 days following exposure to fibroblast growth factor-2 as well as mechanical stress (35,36).…”

Section: Discussionmentioning

confidence: 99%

“…Two features of human bone marrow-derived MSCs (hMSC) suggest that they may be the precursors of the myofibroblasts found in the tumor stroma: (a) MSCs develop characteristics of myofibroblasts, such as expression of a-SMA, under defined tissue culture conditions (13); (b) MSCs isolated from the bone marrow and labeled ex vivo localize to solid tumors after i.v. administration in animal models (8,14,15).…”

Section: Introductionmentioning

confidence: 99%

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Carcinoma-Associated Fibroblast–Like Differentiation of Human Mesenchymal Stem Cells

et al. 2008

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Carcinoma-associated fibroblasts (CAF) have recently been implicated in important aspects of epithelial solid tumor biology, such as neoplastic progression, tumor growth, angiogenesis, and metastasis. However, neither the source of CAFs nor the differences between CAFs and fibroblasts from nonneoplastic tissue have been well defined. In this study, we show that human bone marrow-derived mesenchymal stem cells (hMSCs) exposed to tumor-conditioned medium (TCM) over a prolonged period of time assume a CAF-like myofibroblastic phenotype. More importantly, these cells exhibit functional properties of CAFs, including sustained expression of stromal-derived factor-1 (SDF-1) and the ability to promote tumor cell growth both in vitro and in an in vivo coimplantation model, and expression of myofibroblast markers, including A-smooth muscle actin and fibroblast surface protein. hMSCs induced to differentiate to a myofibroblast-like phenotype using 5-azacytidine do not promote tumor cell growth as efficiently as hMSCs cultured in TCM nor do they show increased SDF-1 expression. Furthermore, gene expression profiling revealed similarities between TCM-exposed hMSCs and CAFs. Taken together, these data suggest that hMSCs are a source of CAFs and can be used in the modeling of tumor-stroma interactions. To our knowledge, this is the first report showing that hMSCs become activated and resemble carcinoma-associated myofibroblasts on prolonged exposure to conditioned medium from MDAMB231 human breast cancer cells. [Cancer Res 2008;68(11):4331-9]

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Carcinoma-Associated Fibroblast–Like Differentiation of Human Mesenchymal Stem Cells

et al. 2008

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“…Moreover, the morphology of MSCs was reported to be fibroblast-like [43], [44]. Bone marrow-derived MSCs selectively express FAP but not other resources [45], and slightly express α-SMA [46]. But MSCs in tumor stroma are currently not reported to express these two markers.…”

Section: Discussionmentioning

confidence: 99%

CD117 Expression in Fibroblasts-Like Stromal Cells Indicates Unfavorable Clinical Outcomes in Ovarian Carcinoma Patients

Huang

Yuan

et al. 2014

PLoS ONE

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The stem cell factor (SCF) receptor CD117 (c-kit), is widely used for identification of hematopoietic stem cells and cancer stem cells. Moreover, CD117 expression in carcinoma cells indicates a poor prognosis in a variety of cancers. However the potential expression in tumor microenvironment and the biological and clinical impact are currently not reported. The expression of CD117 was immunohistochemically evaluated in a serial of 242 epithelial ovarian cancer (EOC) cases. Thirty-eight out of 242 cases were CD117 positive in fibroblast-like stromal cells and 22 cases were positive in EOC cells. Four cases were both positive in fibroblast-like stromal cells and EOC cells for CD117. CD117 expression in fibroblast-like stromal cells in ovarian carcinoma was closely linked to advanced FIGO stage, poor differentiation grade and histological subtype (p<0.05), and it was significantly associated with poor overall survival (OS) and progression free survival (PFS) (Kaplan-Meier analysis; p<0.05, log-rank test). CD117 expression in ovarian carcinoma cells was not associated with these clinicopathological variables. The CD117 positive fibroblast-like stromal cells were all positive for mesenchymal stem/stromal cell (MSC) marker CD73 but negative for fibroblast markers fibroblast activation protein (FAP) and α smooth muscle actin (α-SMA), indicating that the CD117+/CD73+ fibroblast-like stromal cells are a subtype of mesenchymal stem cells in tumor stroma, although further characterization of these cells are needed. It is concluded herewith that the presence of CD117+/CD73+ fibroblast-like stromal cells in ovarian carcinoma is an unfavorable clinical outcome indication.

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“…28,29,46,47 These cells were characterized by the expression of surface markers, including CD105, 28,48,49 vascular cell adhesion protein 1 (VCAM-1, also known as CD106), 26,30 CD166, 8,28,48 Notch 1, 9,30,36 STRO-1 9,30,43 and smooth-muscle actin. 50 For example, Lotz et al . reported a high percentage (>45%) of cells positive for Notch-1, STRO-1 and VCAM-1 throughout normal cartilage, mostly in the superficial zone.…”

Section: Origin Of Cspcsmentioning

confidence: 99%

Origin and function of cartilage stem/progenitor cells in osteoarthritis

2014

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Articular cartilage is a physiologically non-self-renewing avascular tissue with a singular cell type, the chondrocyte, which functions as the load-bearing surface of the arthrodial joint. Injury to cartilage often progresses spatiotemporally from the articular surface to the subchondral bone, leading to development of degenerative joint diseases such as osteoarthritis (OA). Although lacking intrinsic reparative ability, articular cartilage has been shown to contain a population of stem cells or progenitor cells, similar to those found in many other adult tissues, that are thought to be involved in the maintenance of tissue homeostasis. These so-called cartilage-derived stem/progenitor cells (CSPCs) have been observed in human, equine and bovine articular cartilage, and have been identified, isolated and characterized on the basis of expression of stem-cell-related surface markers, clonogenicity and multilineage differentiation ability. However, the origin and functions of CSPCs are incompletely understood. We review here the current status of CSPC research and discuss the possible origin of these cells, what role they might have in cartilage repair, and their therapeutic potential in OA.

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Alpha-smooth muscle actin expression and structure integrity in chondrogenesis of human mesenchymal stem cells

Cited by 17 publications

References 35 publications

Carcinoma-Associated Fibroblast–Like Differentiation of Human Mesenchymal Stem Cells

Carcinoma-Associated Fibroblast–Like Differentiation of Human Mesenchymal Stem Cells

CD117 Expression in Fibroblasts-Like Stromal Cells Indicates Unfavorable Clinical Outcomes in Ovarian Carcinoma Patients

Origin and function of cartilage stem/progenitor cells in osteoarthritis

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